tbuckley/cabot-search huggingface dataset:
A Facile Crystallization Strategy to Turn Calcium Bisphosphonates into Novel Osteogenesis‐Inducing Biomaterials
Authors: Chen Zhuang, Guanglin Zhu, Yingjun Wang, Lin Wang, Xuetao Shi, Chuanbin Mao
Journal: Advanced Healthcare Materials (2023)

Insoluble metal bisphosphonates (BPs) are considered an ideal alternative to the soluble counterparts in regenerative medicine due to their increased BP release profile, but still present undesired properties (e.g., low stability, uncontrolled degradation, and poor biocompatibility). Through a simple crystallization on a solid calcium hydroxyapatite (HA)-based substrate from a BP precursor solution in 30 days, a series of insoluble calcium BP (CaBP) crystals are developed. These crystals, including calcium alendronate (CaAln), calcium pamidronate (CaPam), calcium incadronate (CaInc), calcium risedronate (CaRis), calcium zoledronate (CaZol), and calcium di-minodronate (Ca(Min)
External Control Arms and Data Analysis Methods in Nonrandomized Trial of Patients With Glioblastoma
Authors: Rifaquat Rahman, Steffen Ventz, Lorenzo Trippa
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
YAP/TEAD1 and β‐catenin/LEF1 synergistically induce estrogen receptor α to promote osteogenic differentiation of bone marrow stromal cells
Authors: Peiqi Wang, Lingyi Huang, Fan Yang, Wanxi Chen, Ding Bai, Yongwen Guo
Journal: MedComm (2023)

Abstract Bone remodeling is vital to the maintenance of bone homeostasis and may lead to destructive skeletal diseases once the balance is disrupted. Crosstalk between Wnt and estrogen receptor (ER) signaling has been proposed in bone remodeling, but the underlying mechanism remains unclear. This study was designed to explore the effect of Wnt‐ER signaling during the osteogenic differentiation of bone marrow stromal cells (BMSCs). Rat BMSCs were isolated and identified using flow cytometry and stimulated with Wnt3a. Wnt3a treatment promoted osteogenic differentiation and mineralization of the BMSCs. Meanwhile, Wnt3a enhanced the expression of ERα as well as the canonical Wnt signaling mediator β‐catenin and the alternative Wnt signaling effector Yes‐associated protein 1 (YAP1). Interestingly, DNA pulldown assay revealed direct binding of transcriptional enhanced associate domain 1 (TEAD1) and lymphoid enhancer binding factor 1 (LEF1), transcriptional partners of YAP1 and β‐catenin, respectively, to the promoter region of ERα. In addition, inhibition of TEAD1 and LEF1 suppressed Wnt3‐promoted BMSC osteogenic differentiation and blocked Wnt3a‐induced ERα expression. Furthermore, an in vivo model of femoral bone defect also supported that Wnt3a facilitated bone healing in an ERα‐dependent way. Together, we suggest that Wnt3a promotes the osteogenic activity of BMSCs through YAP1 and β‐catenin‐dependent activation of ERα, via direct binding of TEAD1 and LEF1 to the ERα promoter.
UTX inactivation in germinal center B cells promotes the development of multiple myeloma with extramedullary disease
Authors: Ola Rizq, Naoya Mimura, Motohiko Oshima, Shuji Momose, Naoya Takayama, Naoki Itokawa, Shuhei Koide, Asuka Shibamiya, Yurie Miyamoto-Nagai, Mohamed Rizk, Yaeko Nakajima-Takagi, Kazumasa Aoyama, Changshan Wang, Atsunori Saraya, Ryoji Ito, Masanori Seimiya, Mariko Watanabe, Satoshi Yamasaki, Tatsuhiro Shibata, Kiyoshi Yamaguchi, Yoichi Furukawa, Tetsuhiro Chiba, Emiko Sakaida, Chiaki Nakaseko, Jun-ichi Tamaru, Yu-Tzu Tai, Kenneth C. Anderson, Hiroaki Honda, Atsushi Iwama
Journal: Leukemia (2023)

UTX/KDM6A, a histone H3K27 demethylase and a key component of the COMPASS complex, is frequently lost or mutated in cancer; however, its tumor suppressor function remains largely uncharacterized in multiple myeloma (MM). Here, we show that the conditional deletion of the X-linked Utx in germinal center (GC) derived cells collaborates with the activating BrafV600E mutation and promotes induction of lethal GC/post-GC B cell malignancies with MM-like plasma cell neoplasms being the most frequent. Mice that developed MM-like neoplasms showed expansion of clonal plasma cells in the bone marrow and extramedullary organs, serum M proteins, and anemia. Add-back of either wild-type UTX or a series of mutants revealed that cIDR domain, that forms phase-separated liquid condensates, is largely responsible for the catalytic activity-independent tumor suppressor function of UTX in MM cells. Utx loss in concert with BrafV600E only slightly induced MM-like profiles of transcriptome, chromatin accessibility, and H3K27 acetylation, however, it allowed plasma cells to gradually undergo full transformation through activation of transcriptional networks specific to MM that induce high levels of Myc expression. Our results reveal a tumor suppressor function of UTX in MM and implicate its insufficiency in the transcriptional reprogramming of plasma cells in the pathogenesis of MM.
AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma
Authors: Amit G. Singal, Josep M. Llovet, Mark Yarchoan, Neil Mehta, Julie K. Heimbach, Laura A. Dawson, Janice H. Jou, Laura M. Kulik, Vatche G. Agopian, Jorge A. Marrero, Mishal Mendiratta-Lala, Daniel B. Brown, William S. Rilling, Lipika Goyal, Alice C. Wei, Tamar H. Taddei
Journal: Hepatology (2023)

Singal, Amit G.; Llovet, Josep M.; Yarchoan, Mark; Mehta, Neil; Heimbach, Julie K.; Dawson, Laura A.; Jou, Janice H.; Kulik, Laura M.; Agopian, Vatche G.; Marrero, Jorge A.; Mendiratta-Lala, Mishal; Brown, Daniel B.; Rilling, William S.; Goyal, Lipika; Wei, Alice C.; Taddei, Tamar H. Author Information
<i>INKILN</i> is a Novel Long Noncoding RNA Promoting Vascular Smooth Muscle Inflammation via Scaffolding MKL1 and USP10
Authors: Wei Zhang, Jinjing Zhao, Lin Deng, Nestor Ishimwe, Jessica Pauli, Wen Wu, Shengshuai Shan, Wolfgang Kempf, Margaret D. Ballantyne, David Kim, Qing Lyu, Matthew Bennett, Julie Rodor, Adam W. Turner, Yao Wei Lu, Ping Gao, Mihyun Choi, Ganesh Warthi, Ha Won Kim, Margarida M. Barroso, William B. Bryant, Clint L. Miller, Neal L. Weintraub, Lars Maegdefessel, Joseph M. Miano, Andrew H Baker, Xiaochun Long
Journal: Circulation (2023)

Activation of vascular smooth muscle cell (VSMC) inflammation is vital to initiate vascular disease. The role of human-specific long noncoding RNAs in VSMC inflammation is poorly understood.
Legal Penalties for Physicians Providing Gender-Affirming Care
Authors: Christy Mallory, Madeline G. Chin, Justine C. Lee
Journal: JAMA (2023)

This Viewpoint explains the “legal limbo” physicians may find themselves in, straddling state laws banning gender-affirming care and federal nondiscrimination law, both of which remain unclear due to ongoing legal challenges in the courts.
Celloscope: a probabilistic model for marker-gene-driven cell type deconvolution in spatial transcriptomics data
Authors: Agnieszka Geras, Shadi Darvish Shafighi, Kacper Domżał, Igor Filipiuk, Alicja Rączkowska, Paulina Szymczak, Hosein Toosi, Leszek Kaczmarek, Łukasz Koperski, Jens Lagergren, Dominika Nowis, Ewa Szczurek
Journal: Genome biology (2023)

Abstract Spatial transcriptomics maps gene expression across tissues, posing the challenge of determining the spatial arrangement of different cell types. However, spatial transcriptomics spots contain multiple cells. Therefore, the observed signal comes from mixtures of cells of different types. Here, we propose an innovative probabilistic model, Celloscope, that utilizes established prior knowledge on marker genes for cell type deconvolution from spatial transcriptomics data. Celloscope outperforms other methods on simulated data, successfully indicates known brain structures and spatially distinguishes between inhibitory and excitatory neuron types based in mouse brain tissue, and dissects large heterogeneity of immune infiltrate composition in prostate gland tissue.
New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine
Authors: Hanli Xu, Shuye Lin, Ziyun Zhou, Duoduo Li, Xiting Zhang, Muhan Yu, Ruoyi Zhao, Yiheng Wang, Junru Qian, Xinyi Li, Bohan Li, Chuhan Wei, Keqiang Chen, Teizo Yoshimura, Ji Ming Wang, Jiaqiang Huang
Journal: Cellular and Molecular Immunology (2023)

Abstract Over the past thirty years, the importance of chemokines and their seven-transmembrane G protein-coupled receptors (GPCRs) has been increasingly recognized. Chemokine interactions with receptors trigger signaling pathway activity to form a network fundamental to diverse immune processes, including host homeostasis and responses to disease. Genetic and nongenetic regulation of both the expression and structure of chemokines and receptors conveys chemokine functional heterogeneity. Imbalances and defects in the system contribute to the pathogenesis of a variety of diseases, including cancer, immune and inflammatory diseases, and metabolic and neurological disorders, which render the system a focus of studies aiming to discover therapies and important biomarkers. The integrated view of chemokine biology underpinning divergence and plasticity has provided insights into immune dysfunction in disease states, including, among others, coronavirus disease 2019 (COVID-19). In this review, by reporting the latest advances in chemokine biology and results from analyses of a plethora of sequencing-based datasets, we outline recent advances in the understanding of the genetic variations and nongenetic heterogeneity of chemokines and receptors and provide an updated view of their contribution to the pathophysiological network, focusing on chemokine-mediated inflammation and cancer. Clarification of the molecular basis of dynamic chemokine-receptor interactions will help advance the understanding of chemokine biology to achieve precision medicine application in the clinic.
PCK1 Protects against Mitoribosomal Defects in Diabetic Nephropathy in Mouse Models
Authors: Kazuhiro Hasegawa, Yusuke Sakamaki, Masanori Tamaki, Shu Wakino
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Renal gluconeogenesis plays an important role in the pathogenesis of diabetic nephropathy (DN). Proximal tubular phosphoenolpyruvate carboxykinase1 (PEPCK1) is the rate-limiting enzyme in gluconeogenesis. However, the functions of PEPCK1 have not been elucidated. We describe the novel role of PEPCK1 as a mitoribosomal protector using Pck1 transgenic (TG) mice and knockout mice. Pck1 blocks excessive glycolysis by suppressing the upregulation of excess HK2 (the rate-limiting enzyme of glycolysis). Notably, Pck1 overexpression retains mitoribosomal function and suppresses renal fibrosis. The renal and mitoribosomal protective roles of Pck1 may provide important clues for understanding DN pathogenesis and provide novel therapeutic targets. Background Phosphoenolpyruvate carboxykinase (PEPCK) is part of the gluconeogenesis pathway, which maintains fasting glucose levels and affects renal physiology. PEPCK consists of two isoforms—PEPCK1 and PEPCK2—that the Pck1 and Pck2 genes encode. Gluconeogenesis increases in diabetic nephropathy (DN), escalating fasting and postprandial glucose levels. Sodium–glucose cotransporter-2 inhibitors increase hepatic and renal gluconeogenesis. We used genetically modified mice to investigate whether renal gluconeogenesis and Pck1 activity are renoprotective in DN. Methods We investigated the expression of Pck1 in the proximal tubule (PTs) of streptozotocin (STZ)-treated diabetic mice. We studied the phenotypic changes in PT-specific transgenic (TG) mice and PT-specific Pck1 conditional knockout (CKO) mice. Results The expression of Pck1 in PTs was downregulated in STZ-treated diabetic mice when they exhibited albuminuria. TG mice overexpressing Pck1 had improved albuminuria, concomitant with the mitigation of PT cell apoptosis and deposition of peritubular type IV collagen. Moreover, CKO mice exhibited PT cell apoptosis and type IV collagen deposition, findings also observed in STZ-treated mice. Renal fibrotic changes in CKO mice were associated with increasing defects in mitochondrial ribosomes (mitoribosomes). The TG mice were protected against STZ-induced mitoribosomal defects. Conclusion PCK1 preserves mitoribosomal function and may play a novel protective role in DN.
Letter to the Editor: People living with HIV and NAFLD—A population left behind in the global effort for liver fibrosis screening?
Authors: Giada Sebastiani, Jovana Milic, Emmanuel A. Tsochatzis, Catia Marzolini, Michael Betel, Sanjay Bhagani, Caryn G. Morse, Felice Cinque, James B. Maurice, Patrick Ingiliz, Jennifer Price, Maud Lemoine, Jürgen K. Rockstroh, Giovanni Guaraldi
Journal: Hepatology (2023)

Sebastiani, Giada; Milic, Jovana; Tsochatzis, Emmanuel A.; Marzolini, Catia; Betel, Michael; Bhagani, Sanjay; Morse, Caryn G.; Cinque, Felice; Maurice, James B.; Ingiliz, Patrick; Price, Jennifer; Lemoine, Maud; Rockstroh, Jürgen K.; Guaraldi, Giovanni; on behalf of the Steatohepatitis in HIV Emerging Research (SHIVER) Network Author Information
Comparison of Anti–Programmed Cell Death Ligand 1 Therapy Combinations vs Sunitinib for Metastatic Renal Cell Carcinoma
Authors: Brigida Anna Maiorano, Davide Ciardiello, Evaristo Maiello, Giandomenico Roviello
Journal: JAMA Network Open (2023)

This meta-analysis of 3 randomized clinical trials evaluates the association of combined anti–PD-L1 agents with survival and response rate among patients with metastatic renal cell carcinoma.
CD301b+ macrophage: the new booster for activating bone regeneration in periodontitis treatment
Authors: Can Wang, Qin Zhao, Chen Chen, Jiaojiao Li, Jing Zhang, Shuyuan Qu, Hua Tang, Hao Zeng, Yufeng Zhang
Journal: International Journal of Oral Science (2023)

Abstract Periodontal bone regeneration is a major challenge in the treatment of periodontitis. Currently the main obstacle is the difficulty of restoring the regenerative vitality of periodontal osteoblast lineages suppressed by inflammation, via conventional treatment. CD301b + macrophages were recently identified as a subpopulation that is characteristic of a regenerative environment, but their role in periodontal bone repair has not been reported. The current study indicates that CD301b + macrophages may be a constituent component of periodontal bone repair, and that they are devoted to bone formation in the resolving phase of periodontitis. Transcriptome sequencing suggested that CD301b + macrophages could positively regulate osteogenesis-related processes. In vitro, CD301b + macrophages could be induced by interleukin 4 (IL-4) unless proinflammatory cytokines such as interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were present. Mechanistically, CD301b + macrophages promoted osteoblast differentiation via insulin-like growth factor 1 (IGF-1)/thymoma viral proto-oncogene 1 (Akt)/mammalian target of rapamycin (mTOR) signaling. An osteogenic inducible nano-capsule (OINC) consisting of a gold nanocage loaded with IL-4 as the “core” and mouse neutrophil membrane as the “shell” was designed. When injected into periodontal tissue, OINCs first absorbed proinflammatory cytokines in inflamed periodontal tissue, then released IL-4 controlled by far-red irradiation. These events collectively promoted CD301b + macrophage enrichment, which further boosted periodontal bone regeneration. The current study highlights the osteoinductive role of CD301b + macrophages, and suggests a CD301b + macrophage-targeted induction strategy based on biomimetic nano-capsules for improved therapeutic efficacy, which may also provide a potential therapeutic target and strategy for other inflammatory bone diseases.
Results from Expanded Access Programs: A Review of Academic Literature
Authors: Tobias B. Polak, David G. J. Cucchi, Jasmin Schelhaas, Syed S. Ahmed, Naima Khoshnaw, Joost van Rosmalen, Carin A. Uyl-de Groot
Journal: Drugs (2023)

Although expanded access is an increasingly used pathway for patients to access investigational medicine, little is known on the magnitude and content of published scientific research collected via expanded access.We performed a review of all peer-reviewed expanded access publications between January 1, 2000 and January 1, 2022. We analyzed the publications for drugs, diseases, disease area, patient numbers, time, geographical location, subject, and research methodology (single center/multicenter, international/national, prospective/retrospective). We additionally analyzed endpoints reported in all COVID-19-related expanded access publications.We screened 3810 articles and included 1231, describing 523 drugs for 354 diseases for 507,481 patients. The number of publications significantly increased over time ([Formula: see text]). Large geographical disparities existed as Europe and the Americas accounted for 87.4% of all publications, whereas Africa only accounted for 0.6%. Oncology and hematology accounted for 53% of all publications. Twenty-nine percent of all expanded access patients (N = 197,187) reported on in 2020 and 2021 were treated in the context of COVID-19.By summarizing characteristics of patients, diseases, and research methods described in all scientific literature published on expanded access, we provide a unique dataset for future research. We show that published scientific research on expanded access has surged over the past decades, partly due to COVID-19. However, international collaboration and equity in geographic access remain an issue of concern. Lastly, we stress the need for harmonization of research legislation and guidance on the value of expanded access data within real-world data frameworks to improve equity in patient access and streamline future expanded access research.
Incidence and Outcomes of Non–Ventilator-Associated Hospital-Acquired Pneumonia in 284 US Hospitals Using Electronic Surveillance Criteria
Authors: Barbara E. Jones, Aaron L. Sarvet, Jian Ying, Robert Jin, McKenna R. Nevers, Sarah E. Stern, Aileen Ocho, Caroline McKenna, Laura E. McLean, Matthew A. Christensen, Russell E. Poland, Jeffrey S. Guy, Kenneth E. Sands, Chanu Rhee, Jessica G. Young, Michael Klompas
Journal: JAMA Network Open (2023)

Non-ventilator-associated hospital-acquired pneumonia (NV-HAP) is a common and deadly hospital-acquired infection. However, inconsistent surveillance methods and unclear estimates of attributable mortality challenge prevention.
Association of Allostatic Load With All-Cause Mortality in Patients With Breast Cancer
Authors: Samilia Obeng-Gyasi, Mohamed I. Elsaid, Yurong Lu, JC Chen, William E. Carson, Tarah J. Ballinger, Barbara L. Andersen
Journal: JAMA Network Open (2023)

Elevated allostatic load (AL) has been associated with adverse socioenvironmental stressors and tumor characteristics that convey poor prognosis in patients with breast cancer. Currently, the association between AL and all-cause mortality in patients with breast cancer is unknown.To examine the association between AL and all-cause mortality in patients with breast cancer.This cohort study used data from an institutional electronic medical record and cancer registry at the National Cancer Institute Comprehensive Cancer Center. Participants were patients with breast cancer diagnoses (stage I-III) between January 1, 2012, through December 31, 2020. Data were analyzed from April 2022 through November 2022.AL was expressed as a summary score calculated by assigning 1 point for biomarkers in the worst sample quartile. High AL was defined as AL greater than the median.The main outcome was all-cause mortality. A Cox proportional hazard models with robust variance tested the association between AL and all-cause mortality.There were 4459 patients (median [IQR] age, 59 [49-67] years) with an ethnoracial distribution of 3 Hispanic Black patients (0.1%), 381 non-Hispanic Black patients (8.5%), 23 Hispanic White patients (0.5%), 3861 non-Hispanic White patients (86.6%), 27 Hispanic patients with other race (0.6%), and 164 non-Hispanic patients with other race (3.7%). The mean (SD) AL was 2.6 (1.7). Black patients (adjusted relative ratio [aRR], those with 1.11; 95% CI, 1.04-1.18), single marital status (aRR, 1.06; 95% CI, 1.00-1.12), and those with government-supplied insured (Medicaid aRR, 1.14; 95% CI, 1.07-1.21; Medicare aRR, 1.11; 95% CI, 1.03-1.19) had a higher adjusted mean AL than those who were White, married/living as married, or privately insured, respectively. Adjusting for sociodemographic, clinical, and treatment factors, high AL was associated with a 46% increase in mortality risk (hazard ratio [HR], 1.46; 95% CI, 1.11-1.93) over low AL. Similarly, compared with patients in the first AL quartile, those in the third quartile (HR, 1.53; 95% CI, 1.07-2.18) and the fourth quartile (HR, 1.79; 95% CI, 1.16-2.75) had significantly increased risks of mortality. There was a significant dose-dependent association between increased AL and a higher risk of all-cause mortality. Furthermore, AL remained significantly associated with higher all-cause mortality after adjusting for the Charlson Comorbidity Index.These findings suggest increased AL is reflective of socioeconomic marginalization and associated with all-cause mortality in patients with breast cancer.
Real‐Time Micromotor Probe for Immune Neutrophil Activation State
Authors: Dongmei Fu, Jiamiao Jiang, Shaoming Fu, Dazhi Xie, Chao Gao, Ye Feng, Suyi Liu, Yicheng Ye, Lu Liu, Yingfeng Tu, Fei Peng
Journal: Advanced Healthcare Materials (2023)

Abstract Neutrophil activation is a hallmark of the immune response. Approaches to identify neutrophil activation in real time are necessary but are still lacking. In this study, magnetic Spirulina micromotors are used as label‐free probes that exhibit differences in motility under different neutrophil activation states. This is correlated with different secretions into the extracellular environment by activated/non‐activated cells and local environmental viscoelasticity. The micromotor platform can bypass non‐activated immune cells while being stopped by activated cells. Thus, the micromotors can serve as label‐free biomechanical probes of the immune cell state. They can detect the activation state of target immune cells in real time and with single‐cell precision, which provides new ideas for the diagnosis and treatment of diseases while deepening understanding of the biomechanics of activated immune cells.